The proposed research is intended to answer several questions: (1) What is the basis of the defective replication of human adenoviruses in nonpermissive monkey cells? (2) What is the mechanism by which another virus, simian virus 40 (SV40) overcomes the nonpermissive state and enhances adenovirus replication? (3) What are some of the mechanisms of latency or persistence which can be overcome by superinfection with other viruses? (4) What are the means by which cells prevent the efficient replication of viruses within them? (5) What is the relationship between nonpermissive infection and oncogenic transformation? The first three of these questions represent a continuaion of work which is currently in progress in my laboratory. The fourth and fifth questions are a natural extension of this work. We will concentrate on mechanisms intrinsic to the cell, excluding effects of antibody and alteration of cell surface receptors. It is hoped that these studies will provide useful information on the cell specificity of virus infectivity and oncogenesis as well as yielding insights as to the ways viruses may cooperate to alter virus-cell interactions.